INTRODUCTION 1
The Origins of Organic Chemistry 1
Berzelius，Wohler，and Vitalism 1
The Structural Theory 3
Electronic Theories of Structure and Reactivity 3
The Influence of Organic Chemistry 4
Computers and Organic Chemistry 4
Challenges and Opportunities 5
Where Did the Carbon Come From？ 6
CHAPTER 1 STRUCTURE DETERMINES PROPERTIES 7
1.1 Atoms，Electrons，and Orbitals 7
1.2 Ionic Bonds 10
1.3 Covalent Bonds and the Octet Rule 12
1.4 Double Bonds and Triple Bonds 14
1.5 Polar Covalent Bonds and Electronegativity 14
Electrostatic Potential Maps 16
1.6 Formal Charge 17
1.7 Structural Formulas of Organic Molecules 21
1.8 Constitutional Isomers 23
1.9 Resonance 24
Learning By Modeling 28
1.10 The Shapes of Some Simple Molecules 29
1.11 Molecular Dipole Moments 31
1.12 Acids and Bases：The Arrhenius View 32
1.13 Acids and Bases：The Bronsted-Lowry View 33
Curved Arrows 34
1.14 What Happened to pKb？ 37
1.15 How Structure Affects Acid Strength 38
1.16 Acid-Base Equilibria 43
1.17 Lewis Acids and Lewis Bases 45
1.18 SUMMARY 47
Problems 50
CHAPTER 2 HYDROCARBON FRAMEWORKS.ALKANES 57
2.1 Classes of Hydrocarbons 57
2.2 Electron Waves and Chemical Bonds 58
2.3 Bonding in H2：The Valence Bond Model 60
2.4 Bonding in H2：The Molecular Orbital Model 61
2.5 Introduction to Alkanes：Methane，Ethane，and Propane 63
2.6 sp3 Hybridization and Bonding in Methane 63
Methane and the Biosphere 66
2.7 Bonding in Ethane 67
2.8 Isomeric Alkanes：The Butanes 67
2.9 Higher n-Alkanes 68
2.10 The C5H12 Isomers 69
2.11 IUPAC Nomenclature of Unbranched Alkanes 70
2.12 Applying the IUPAC Rules：The Names of the C6H14 Isomers 71
2.13 Alkyl Groups 73
2.14 IUPAC Names of Highly Branched Alkanes 75
2.15 Cycloalkane Nomenclature 77
A Brief History of Systematic Organic Nomenclature 78
2.16 Sources of Alkanes and Cycloalkanes 79
2.17 Physical Properties of Alkanes and Cycloalkanes 80
2.18 Chemical Properties.Combustion of Alkanes 83
Thermochemistry 86
2.19 Oxidation-Reduction in Organic Chemistry 87
2.20 sp2 Hybridization and Bonding in Ethylene 89
2.21 sp Hybridization and Bonding in Acetylene 92
2.22 Which Theory of Chemical Bonding Is Best？ 93
2.23 SUMMARY 95
Problems 99
CHAPTER 3 CONFORMATIONS OF ALKANES AND CYCLOALKANES 104
3.1 Conformational Analysis of Ethane 105
3.2 Conformational Analysis of Butane 109
3.3 Conformations of Higher Alkanes 110
Molecular Mechanics Applied to Alkanes and Cycloalkanes 111
3.4 The Shapes of Cycloalkanes：Planar or Nonplanar？ 112
3.5 Small Rings：Cyclopropane and Cyclobutane 114
3.6 Cyclopentane 115
3.7 Conformations of Cyclohexane 116
3.8 Axial and Equatorial Bonds in Cyclohexane 117
3.9 Conformational Inversion （Ring Flipping） in Cyclohexane 119
3.10 Conformational Analysis of Monosubstituted Cyclohexanes 120
Enthalpy，Free Energy，and Equilibrium Constant 122
3.11 Disubstituted Cycloalkanes：Stereoisomers 124
3.12 Conformational Analysis of Disubstituted Cyclohexanes 125
3.13 Medium and Large Rings 129
3.14 Polycyclic Ring Systems 129
3.15 Heterocyclic Compounds 131
3.16 SUMMARY 132
Problems 136
CHAPTER 4 ALCOHOLS AND ALKYL HALIDES 142
4.1 Functional Groups 143
4.2 IUPAC Nomenclature of Alkyl Halides 144
4.3 IUPAC Nomenclature of Alcohols 145
4.4 Classes of Alcohols and Alkyl Halides 146
4.5 Bonding in Alcohols and Alkyl Halides 146
4.6 Physical Properties of Alcohols and Alkyl Halides：Intermolecular Forces 147
4.7 Preparation of Alkyl Halides from Alcohols and Hydrogen Halides 151
4.8 Mechanism of the Reaction of Alcohols with Hydrogen Halides 153
4.9 Potential Energy Diagrams for Multistep Reactions： 159
The SN1 Mechanism 159
4.10 Structure，Bonding，and Stability of Carbocations 160
4.11 Effect of Alcohol Structure on Reaction Rate 162
4.12 Reaction of Primary Alcohols with Hydrogen Halides：The SN2 Mechanism 163
4.13 Other Methods for Converting Alcohols to Alkyl Halides 165
4.14 Halogenation of Alkanes 166
4.15 Chlorination of Methane 166
4.16 Structure and Stability of Free Radicals 167
4.17 Mechanism of Methane Chlorination 172
4.18 Halogenation of Higher Alkanes 173
From Bond Energies to Heats of Reaction 174
4.19 SUMMARY 178
Problems 182
CHAPTER 5 STRUCTURE AND PREPARATION OF ALKENES：ELIMINATION REACTIONS 187
5.1 Alkene Nomenclature 187
Ethylene 189
5.2 Structure and Bonding in Alkenes 190
5.3 Isomerism in Alkenes 192
5.4 Naming Stereoisomeric Alkenes by the E-Z Notational System 193
5.5 Physical Properties of Alkenes 196
5.6 Relative Stabilities of Alkenes 197
5.7 Cycloalkenes 200
5.8 Preparation of Alkenes：Elimination Reactions 202
5.9 Dehydration of Alcohols 202
5.10 Regioselectivity in Alcohol Dehydration：The Zaitsev Rule 204
5.11 Stereoselectivity in Alcohol Dehydration 205
5.12 The E1 and E2 Mechanisms of Alcohol Dehydration 206
5.13 Rearrangements in Alcohol Dehydration 208
5.14 Dehydrohalogenation of Alkyl Halides 211
5.15 The E2 Mechanism of Dehydrohalogenation of Alkyl Halides 214
5.16 Anti Elimination in E2 Reactions：Stereoelectronic Effects 216
5.17 The E1 Mechanism of Dehydrohaloge nation of Alkyl Halides 217
5.18 SUMMARY 220
Problems 223
CHAPTER 6 REACTIONS OF ALKENES：ADDITION REACTIONS 230
6.1 Hydrogenation of Alkenes 230
6.2 Heats of Hydrogenation 231
6.3 Stereochemistry of Alkene Hydrogenation 234
6.4 Electrophilic Addition of Hydrogen Halides to Alkenes 235
6.5 Regioselectivity of Hydrogen Halide Addition：Markovnikov’s Rule 236
6.6 Mechanistic Basis for Markovnikov’s Rule 238
Rules，Laws，Theories，and the Scientific Method 239
6.7 Carbocation Rearrangements in Hydrogen Halide Addition to Alkenes 241
6.8 Free-Radical Addition of Hydrogen Bromide to Alkenes 242
6.9 Addition of Sulfuric Acid to Alkenes 245
6.10 Acid-Catalyzed Hydration of Alkenes 247
6.11 Hydroboration-Oxidation of Alkenes 250
6.12 Stereochemistry of Hydroboration-Oxidation 252
6.13 Mechanism of Hydroboration-Oxidation 252
6.14 Addition of Halogens to Alkenes 254
6.15 Stereochemistry of Halogen Addition 256
6.16 Mechanism of Halogen Addition to Alkenes：Halonium Ions 256
6.17 Conversion of Alkenes to Vicinal Halohydrins 259
6.18 Epoxidation of Alkenes 260
6.19 Ozonolysis of Alkenes 262
6.20 Introduction to Organic Chemical Synthesis 265
6.21 Reactions of Alkenes with Alkenes：Polymerization 266
Ethylene and Propene：The Most Important Industrial Organic Chemicals 269
6.22 SUMMARY 271
Problems 274
CHAPTER 7 STEREOCHEMISTRY 281
7.1 Molecular Chirality：Enantiomers 281
7.2 The Chirality Center 282
7.3 Symmetry in Achiral Structures 286
7.4 Optical Activity 287
7.5 Absolute and Relative Configuration 289
7.6 The Cahn-Ingold-Prelog R-5 Notational System 290
7.7 Fischer Projections 293
7.8 Properties of Enantiomers 295
Chiral Drugs 296
7.9 Reactions That Create a Chirality Center 297
7.10 Chiral Molecules with Two Chirality Centers 300
7.11 Achiral Molecules with Two Chirality Centers 303
Chirality of Disubstituted Cyclohexanes 305
7.12 Molecules with Multiple Chirality Centers 306
7.13 Reactions That Produce Diastereomers 307
7.14 Resolution of Enantiomers 310
7.15 Stereoregular Polymers 312
7.16 Chirality Centers Other Than Carbon 314
7.17 SUMMARY 315
Problems 318
CHAPTER 8 NUCLEOPHILIC SUBSTITUTION 326
8.1 Functional Group Transformation by Nucleophilic Substitution 326
8.2 Relative Reactivity of Halide Leaving Groups 330
8.3 The SN2 Mechanism of Nucleophilic Substitution 330
8.4 Stereochemistry of SN2 Reactions 331
8.5 How SN2 Reactions Occur 333
8.6 Steric Effects in SN2 Reactions 334
8.7 Nucleophiles and Nucleophilicity 336
An Enzyme-Catalyzed Nucleophilic Substitution of an Alkyl Halide 339
8.8 The SN1 Mechanism of Nucleophilic Substitution 339
8.9 Carbocation Stability and SN1 Reaction Rates 341
8.10 Stereochemistry of SN1 Reactions 342
8.11 Carbocation Rearrangements in SN1 Reactions 344
8.12 Effect of Solvent on the Rate of Nucleophilic Substitution 345
8.13 Substitution and Elimination as Competing Reactions 348
8.14 Sulfonate Esters as Substrates in Nucleophilic Substitution 350
8.15 Looking Back：Reactions of Alcohols with Hydrogen Halides 354
8.16 SUMMARY 355
Problems 357
CHAPTER 9 ALKYN ES 363
9.1 Sources of Alkynes 363
9.2 Nomenclature 364
9.3 Physical Properties of Alkynes 365
9.4 Structure and Bonding in Alkynes：sp Hybridization 365
Natural and “Designed” Enediyne Antibiotics 368
9.5 Acidity of Acetylene and Terminal Alkynes 368
9.6 Preparation of Alkynes by Alkylation of Acetylene and Terminal Alkynes 370
9.7 Preparation of Alkynes by Elimination Reactions 372
9.8 Reactions of Alkynes 374
9.9 Hydrogenation of Alkynes 374
9.10 Metal-Ammonia Reduction of Alkynes 376
9.11 Addition of Hydrogen Halides to Alkynes 377
9.12 Hydration of Alkynes 379
9.13 Addition of Halogens to Alkynes 381
9.14 Ozonolysis of Alkynes 381
9.15 SUMMARY 382
Problems 384
CHAPTER 10 CONJUGATION IN ALKADIENES AND ALLYLIC SYSTEMS 390
10.1 The Allyl Group 390
10.2 Allylic Carbocations 391
10.3 Allylic Free Radicals 395
10.4 Allylic Halogenation 396
10.5 Classes of Dienes 398
10.6 Relative Stabilities of Dienes 399
10.7 Bonding in Conjugated Dienes 400
10.8 Bonding in Allenes 402
10.9 Preparation of Dienes 404
10.10 Addition of Hydrogen Halides to Conjugated Dienes 405
10.11 Halogen Addition to Dienes 407
Diene Polymers 408
10.12 The Diels-Alder Reaction 409
10.13 The π Molecular Orbitals of Ethylene and 1，3-Butadiene 412
10.14 A π Molecular Orbital Analysis of the Diels-Alder Reaction 414
10.15 SUMMARY 415
Problems 418
CHAPTER 11 ARENES AND AROMATICITY 423
11.1 Benzene 424
11.2 Kekule and the Structure of Benzene 424
Benzene，Dreams，and Creative Thinking 426
11.3 A Resonance Picture of Bonding in Benzene 427
11.4 The Stability of Benzene 428
11.5 An Orbital Hybridization View of Bonding in Benzene 430
11.6 The π Molecular Orbitals of Benzene 430
11.7 Substituted Derivatives of Benzene and Their Nomenclature 432
11.8 Polycyclic Aromatic Hydrocarbons 434
Carbon Clusters，Fullerenes，and Nanotubes 436
11.9 Physical Properties of Arenes 438
11.10 Reactions of Arenes：A Preview 438
11.11 The Birch Reduction 438
11.12 Free-Radical Halogenation of Alkylbenzenes 439
11.13 Oxidation of Alkylbenzenes 443
11.14 Nucleophilic Substitution in Benzylic Halides 444
11.15 Preparation of Alkenylbenzenes 446
11.16 Addition Reactions of Alkenylbenzenes 447
11.17 Polymerization of Styrene 449
11.18 Cyclobutadiene and Cyclooctatetraene 449
11.19 Huckel’s Rule 451
11.20 Annulenes 454
11.21 Aromatic Ions 456
11.22 Heterocyclic Aromatic Compounds 460
11.23 Heterocyclic Aromatic Compounds and Huckel’s Rule 462
11.24 SUMMARY 463
Problems 467
CHAPTER 12 REACTIONS OF ARENES：ELECTROPHILIC AROMATIC SUBSTITUTION 473
12.1 Representative Electrophilic Aromatic Substitution Reactions of Benzene 474
12.2 Mechanistic Principles of Electrophilic Aromatic Substitution 474
12.3 Nitration of Benzene 477
12.4 Sulfonation of Benzene 478
12.5 Halogenation of Benzene 480
12.6 Friedel-Crafts Alkylation of Benzene 481
12.7 Friedel-Crafts Acylation of Benzene 484
12.8 Synthesis of Alkylbenzenes by Acylation-Reduction 486
12.9 Rate and Regioselectivity in Electrophilic Aromatic Substitution 488
12.10 Rate and Regioselectivity in the Nitration of Toluene 489
12.11 Rate and Regioselectivity in the Nitration of （TrifIuoromethyl）benzene 492
12.12 Substituent Effects in Electrophilic Aromatic Substitution：Activating Substituents 494
12.13 Substituent Effects in Electrophilic Aromatic Substitution：Strongly Deactivating Substituents 498
12.14 Substituent Effects in Electrophilic Aromatic Substitution：Halogens 500
12.15 Multiple Substituent Effects 502
12.16 Regioselective Synthesis of Disubstituted Aromatic Compounds 504
12.17 Substitution in Naphthalene 506
12.18 Substitution in Hetereocyclic Aromatic Compounds 507
12.19 SUMMARY 508
Problems 512
CHAPTER 13 SPECTROSCOPY 519
13.1 Principles of Molecular Spectroscopy：Electromagnetic Radiation 520
13.2 Principles of Molecular Spectroscopy：Quantized Energy States 521
13.3 Introduction to 1H NMR Spectroscopy 522
13.4 Nuclear Shielding and 1H Chemical Shifts 525
13.5 Effects of Molecular Structure on 1H Chemical Shifts 526
Ring Currents：Aromatic and Antiaromatic 530
13.6 Interpreting 1H NMR Spectra 532
13.7 Spin-Spin Splitting in 1H NMR Spectroscopy 535
13.8 Splitting Patterns：The Ethyl Group 538
13.9 Splitting Patterns：The Isopropyl Group 540
13.10 Splitting Patterns：Pairs of Doublets 541
13.11 Complex Splitting Patterns 543
13.12 1H NMR Spectra of Alcohols 544
13.13 NMR and Conformations 545
Magnetic Resonance Imaging 546
13.14 13C NMR Spectroscopy 547
13.15 13C Chemical Shifts 549
13.16 13C NMR and Peak Intensities 551
13.17 13C—1H Coupling 552
13.18 Using DEPT to Count Hydrogens Attached to 13C 553
Spectra by the Thousands 555
13.19 2D NMR：COSY and HETCOR 556
13.20 Infrared Spectroscopy 559
13.21 Ultraviolet-Visible （UV-VIS） Spectroscopy 565
13.22 Mass Spectrometry 567
Gas Chromatography，GC/MS，and MS/MS 572
13.23 Molecular Formula as a Clue to Structure 573
13.24 SUMMARY 575
Problems 578
CHAPTER 14 ORGANOMETALLIC COMPOUNDS 587
14.1 Organometallic Nomenclature 588
14.2 Carbon-Metal Bonds in Organometallic Compounds 588
14.3 Preparation of Organolithium Compounds 589
14.4 Preparation of Organomagnesium Compounds：Grignard Reagents 591
14.5 Organolithium and Organomagnesium Compounds as Bronsted Bases 592
14.6 Synthesis of Alcohols Using Grignard Reagents 594
14.7 Synthesis of Alcohols Using Organolithium Reagents 597
14.8 Synthesis of Acetylenic Alcohols 597
14.9 Retrosynthetic Analysis 598
14.10 Preparation of Tertiary Alcohols from Esters and Grignard Reagents 601
14.11 Alkane Synthesis Using Organocopper Reagents 602
14.12 An Organozinc Reagent for Cyclopropane Synthesis 604
14.13 Carbenes and Carbenoids 606
14.14 Transition Metal Organometallic Compounds 608
14.15 Ziegler-Natta Catalysis of Alkene Polymerization 610
An Organometallic Compound That Occurs Naturally：Coenzyme B12 611
14.16 SUMMARY 614
Problems 617
CHAPTER 15 ALCOHOLS，DIOLS，AND THIOLS 623
15.1 Sources of Alcohols 623
15.2 Preparation of Alcohols by Reduction of Aldehydes and Ketones 627
15.3 Preparation of Alcohols by Reduction of Carboxylic Acids and Esters 632
15.4 Preparation of Alcohols from Epoxides 632
15.5 Preparation of Diols 633
15.6 Reactions of Alcohols：A Review and a Preview 635
15.7 Conversion of Alcohols to Ethers 635
15.8 Esterification 638
15.9 Esters of Inorganic Acids 640
15.10 Oxidation of Alcohols 641
Economic and Environmental Factors in Organic Synthesis 644
15.11 Biological Oxidation of Alcohols 645
15.12 Oxidative Cleavage of Vicinal Diols 647
15.13 Thiols 648
15.14 Spectroscopic Analysis of Alcohols and Thiols 651
15.15 SUMMARY 653
Problems 657
CHAPTER 16 ETHERS，EPOXIDES，AND SULFIDES 665
16.1 Nomenclature of Ethers，Epoxides，and Sulfides 665
16.2 Structure and Bonding in Ethers and Epoxides 667
16.3 Physical Properties of Ethers 668
16.4 Crown Ethers 668
Polyether Antibiotics 670
16.5 Preparation of Ethers 671
16.6 The Williamson Ether Synthesis 672
16.7 Reactions of Ethers：A Review and a Preview 673
16.8 Acid-Catalyzed Cleavage of Ethers 674
16.9 Preparation of Epoxides：A Review and a Preview 676
16.10 Conversion of Vicinal Halohydrins to Epoxides 676
16.11 Reactions of Epoxides：A Review and a Preview 678
16.12 Nucleophilic Ring-Opening of Epoxides 679
16.13 Acid-Catalyzed Ring-Opening of Epoxides 681
16.14 Epoxides in Biological Processes 684
16.15 Preparation of Sulfides 685
16.16 Oxidation of Sulfides：Sulfoxides and Sulfones 685
16.17 Alkylation of Sulfides：Sulfonium Salts 686
16.18 Spectroscopic Analysis of Ethers，Epoxides，and Sulfides 688
16.19 SUMMARY 691
Problems 695
CHAPTER 17 ALDEHYDES AND KETONES：NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP 703
17.1 Nomenclature 703
17.2 Structure and Bonding：The Carbonyl Group 706
17.3 Physical Properties 708
17.4 Sources of Aldehydes and Ketones 709
17.5 Reactions of Aldehydes and Ketones：A Review and a Preview 712
17.6 Principles of Nucleophilic Addition：Hydration of Aldehydes and Ketones 712
17.7 Cyanohydrin Formation 717
17.8 Acetal Formation 720
17.9 Acetals as Protecting Groups 723
17.10 Reaction with Primary Amines：Imines 724
17.11 Reaction with Secondary Amines：Enamines 727
Imines in Biological Chemistry 728
17.12 The Wittig Reaction 730
17.13 Planning an Alkene Synthesis via the Wittig Reaction 732
17.14 Stereoselective Addition to Carbonyl Groups 734
17.15 Oxidation of Aldehydes 736
17.16 Baeyer-Villiger Oxidation of Ketones 736
17.17 Spectroscopic Analysis of Aldehydes and Ketones 738
17.18 SUMMARY 741
Problems 745
CHAPTER 18 ENOLS AND ENOLATES 755
18.1 The α-Carbon Atom and Its Hydrogens 756
18.2 α Halogenation of Aldehydes and Ketones 757
18.3 Mechanism of α Halogenation of Aldehydes and Ketones 757
18.4 Enolization and Enol Content 759
18.5 Stabilized Enols 761
18.6 Base-Catalyzed Enolization.Enolate Anions 763
18.7 The Haloform Reaction 765
The Haloform Reaction and the Biosynthesis of Trihalomethanes 767
18.8 Some Chemical and Stereochemical Consequences of Enolization 768
18.9 The Aldol Condensation 769
18.10 Mixed Aldol Condensations 774
18.11 Effects of Conjugation in α，β-Unsaturated Aldehydes and Ketones 775
18.12 Conjugate Addition to α，β-Unsaturated Carbonyl Compounds 777
18.13 Addition of Carbanions to α，β-Unsaturated Ketones： 779
The Michael Reaction 779
18.14 Conjugate Addition of Organocopper Reagents to α，β-Unsaturated Carbonyl Compounds 780
18.15 Alkylation of Enolate Anions 781
18.16 SUMMARY 781
Problems 784
CHAPTER 19 CARBOXYLIC ACIDS 791
19.1 Carboxylic Acid Nomenclature 792
19.2 Structure and Bonding 793
19.3 Physical Properties 794
19.4 Acidity of Carboxylic Acids 795
19.5 Salts of Carboxylic Acids 797
Quantitative Relationships Involving Carboxylic Acids 798
19.6 Substituents and Acid Strength 801
19.7 Ionization of Substituted Benzoic Acids 803
19.8 Dicarboxylic Acids 804
19.9 Carbonic Acid 804
19.10 Sources of Carboxylic Acids 806
19.11 Synthesis of Carboxylic Acids by the Carboxylation of Grignard Reagents 806
19.12 Synthesis of Carboxylic Acids by the Preparation and Hydrolysis of Nitriles 808
19.13 Reactions of Carboxylic Acids：A Review and a Preview 809
19.14 Mechanism of Acid-Catalyzed Esterification 810
19.15 Intramolecular Ester Formation：Lactones 814
19.16 α Halogenation of Carboxylic Acids：The Hell-Volhard-Zelinsky Reaction 815
19.17 Decarboxylation of Malonic Acid and Related Compounds 816
19.18 Spectroscopic Analysis of Carboxylic Acids 819
19.19 SUMMARY 821
Problems 824
CHAPTER 20 CARBOXYLIC ACID DERIVATIVES：NUCLEOPHILIC ACYL SUBSTITUTION 830
20.1 Nomenclature of Carboxylic Acid Derivatives 831
20.2 Structure and Reactivity of Carboxylic Acid Derivatives 833
20.3 General Mechanism for Nucleophilic Acyl Substitution 836
20.4 Nucleophilic Substitution in Acyl Chlorides 838
20.5 Preparation of Carboxylic Acid Anhydrides 841
20.6 Reactions of Carboxylic Acid Anhydrides 842
20.7 Sources of Esters 845
20.8 Physical Properties of Esters 846
20.9 Reactions of Esters：A Review and a Preview 846
20.10 Acid-Catalyzed Ester Hydrolysis 848
20.11 Ester Hydrolysis in Base：Saponification 852
20.12 Reaction of Esters with Ammonia and Amines 857
20.13 Thioesters 858
20.14 Preparation of Amides 859
20.15 Lactams 861
20.16 Imides 862
20.17 Hydrolysis of Amides 862
20.18 Preparation of Nitriles 867
Condensation Polymers：Polyamides and Polyesters 868
20.19 Hydrolysis of Nitriles 870
20.20 Addition of Grignard Reagents to Nitriles 871
20.21 Spectroscopic Analysis of Carboxylic Acid Derivatives 872
20.22 SUMMARY 874
Problems 877
CHAPTER 21 ESTER ENOLATES 886
21.1 The Claisen Condensation 887
21.2 Intramolecular Claisen Condensation：The Dieckmann Reaction 890
21.3 Mixed Claisen Condensations 891
21.4 Acylation of Ketones with Esters 892
21.5 Ketone Synthesis via β-Keto Esters 893
21.6 The Acetoacetic Ester Synthesis 894
21.7 The Malonic Ester Synthesis 897
21.8 Barbiturates 900
21.9 Michael Additions of Stabilized Anions 901
21.10 α Deprotonation of Carbonyl Compounds by Lithium Dialkylamides 902
21.11 SUMMARY 905
Problems 908
CHAPTER 22 AMINES 913
22.1 Amine Nomenclature 913
22.2 Structure and Bonding 916
22.3 Physical Properties 918
22.4 Basicity of Amines 919
22.5 Tetraalkylammonium Salts as Phase-Transfer Catalysts 923
Amines as Natural Products 924
22.6 Reactions That Lead to Amines：A Review and a Preview 926
22.7 Preparation of Amines by Alkylation of Ammonia 928
22.8 The Gabriel Synthesis of Primary Alkylamines 929
22.9 Preparation of Amines by Reduction 931
22.10 Reductive Amination 934
22.11 Reactions of Amines：A Review and a Preview 935
22.12 Reaction of Amines with Alkyl Halides 937
22.13 The Hofmann Elimination 938
22.14 Electrophilic Aromatic Substitution in Arylamines 939
22.15 Nitrosation of Alkylamines 943
22.16 Nitrosation of Arylamines 945
22.17 Synthetic Transformations of Aryl Diazonium Salts 946
22.18 Azo Coupling 950
From Dyes to Sulfa Drugs 951
22.19 Spectroscopic Analysis of Amines 951
22.20 SUMMARY 955
Problems 962
CHAPTER 23 ARYL HALIDES 971
23.1 Bonding in Aryl Halides 971
23.2 Sources of Aryl Halides 972
23.3 Physical Properties of Aryl Halides 972
23.4 Reactions of Aryl Halides：A Review and a Preview 973
23.5 Nucleophilic Substitution in Nitro-Substituted Aryl Halides 975
23.6 The Addition-Elimination Mechanism of Nucleophilic Aromatic Substitution 977
23.7 Related Nucleophilic Aromatic Substitution Reactions 980
23.8 The Elimination-Addition Mechanism of Nucleophilic Aromatic Substitution：Benzyne 981
23.9 Diels-Alder Reactions of Benzyne 985
23.10 SUMMARY 986
Problems 988
CHAPTER 24 PHENOLS 993
24.1 Nomenclature 993
24.2 Structure and Bonding 994
24.3 Physical Properties 995
24.4 Acidity of Phenols 996
24.5 Substituent Effects on the Acidity of Phenols 998
24.6 Sources of Phenols 999
24.7 Naturally Occurring Phenols 1001
24.8 Reactions of Phenols：Electrophilic Aromatic Substitution 1002
24.9 Acylation of Phenols 1004
24.10 Carboxylation of Phenols：Aspirin and the Kolbe-Schmitt Reaction 1006
24.11 Preparation of Aryl Ethers 1008
Agent Orange and Dioxin 1009
24.12 Cleavage of Aryl Ethers by Hydrogen Halides 1010
24.13 Claisen Rearrangement of Allyl Aryl Ethers 1011
24.14 Oxidation of Phenols：Quinones 1012
24.15 Spectroscopic Analysis of Phenols 1014
24.16 SUMMARY 1016
Problems 1019
CHAPTER 25 CARBOHYDRATES 1026
25.1 Classification of Carbohydrates 1026
25.2 Fischer Projections and D-L Notation 1027
25.3 The Aldotetroses 1029
25.4 Aldopentoses and Aldohexoses 1030
25.5 A Mnemonic for Carbohydrate Configurations 1032
25.6 Cyclic Forms of Carbohydrates：Furanose Forms 1032
25.7 Cyclic Forms of Carbohydrates：Pyranose Forms 1036
25.8 Mutarotation 1040
25.9 Ketoses 1041
25.10 Deoxy Sugars 1042
25.11 Amino Sugars 1042
25.12 Branched-Chain Carbohydrates 1043
25.13 Glycosides 1043
25.14 Disaccharides 1046
25.15 Polysaccharides 1048
25.16 Cell-Surface Glycoproteins 1050
How Sweet It Is！ 1051
25.17 Carbohydrate Structure Determination 1052
25.18 Reduction of Carbohydrates 1052
25.19 Oxidation of Carbohydrates 1053
25.20 Cyanohydrin Formation and Chain Extension 1055
25.21 Epimerization，Isomerization，and Retro-Aldol Cleavage 1056
25.22 Acylation and Alkylation of Hydroxyl Groups in Carbohydrates 1058
25.23 Periodic Acid Oxidation of Carbohydrates 1059
25.24 SUMMARY 1061
Problems 1065
CHAPTER 26 LIPIDS 1069
26.1 Acetyl Coenzyme A 1070
26.2 Fats，Oils，and Fatty Acids 1071
26.3 Fatty Acid Biosynthesis 1075
26.4 Phospholipids 1077
26.5 Waxes 1079
26.6 Prostaglandins 1080
Nonsteroidal Antiinflammatory Drugs （NSAIDs） and COX-2 Inhibitors 1083
26.7 Terpenes：The Isoprene Rule 1084
26.8 Isopentenyl Pyrophosphate：The Biological Isoprene Unit 1087
26.9 Carbon-Carbon Bond Formation in Terpene Biosynthesis 1087
26.10 The Pathway from Acetate to Isopentenyl Pyrophosphate 1091
26.11 Steroids：Cholesterol 1093
Good Cholesterol？ Bad Cholesterol？ What’s the Difference？ 1096
26.12 Vitamin D 1096
26.13 Bile Acids 1097
26.14 Corticosteroids 1098
26.15 Sex Hormones 1098
Anabolic Steroids 1099
26.16 Carotenoids 1100
26.17 SUMMARY 1101
Problems 1103
CHAPTER 27 AMINO ACIDS，PEPTIDES，AND PROTEINS 1109
27.1 Classification of Amino Acids 1110
27.2 Stereochemistry of Amino Acids 1115
27.3 Acid-Base Behavior of Amino Acids 1117
Electrophoresis 1120
27.4 Synthesis of Amino Acids 1121
27.5 Reactions of Amino Acids 1123
27.6 Some Biochemical Reactions of Amino Acids 1123
27.7 Peptides 1126
27.8 Introduction to Peptide Structure Determination 1129
27.9 Amino Acid Analysis 1130
27.10 Partial Hydrolysis of Peptides 1130
27.11 End Group Analysis 1131
27.12 Insulin 1131
27.13 The Edman Degradation and Automated Sequencing of Peptides 1133
27.14 The Strategy of Peptide Synthesis 1135
27.15 Amino Group Protection 1137
27.16 Carboxyl Group Protection 1138
27.17 Peptide Bond Formation 1139
27.18 Solid-Phase Peptide Synthesis：The Merrifield Method 1141
27.19 Secondary Structures of Peptides and Proteins 1143
27.20 Tertiary Structure of Peptides and Proteins 1145
27.21 Coenzymes 1147
27.22 Protein Quaternary Structure：Hemoglobin 1148
Oh NO！ It’s Inorganic！ 1149
27.23 SUMMARY 1150
Problems 1152
CHAPTER 28 NUCLEOSIDES，NUCLEOTIDES，AND NUCLEIC ACIDS 1155
28.1 Pyrimidines and Purines 1155
28.2 Nucleosides 1158
28.3 Nucleotides 1160
28.4 Bioenergetics 1162
28.5 ATP and Bioenergetics 1162
28.6 Phosphodiesters，Oligonucleotides，and Polynucleotides 1164
28.7 Nucleic Acids 1165
28.8 Secondary Structure of DNA：The Double Helix 1166
“It Has Not Escaped Our Notice…” 1167
28.9 Tertiary Structure of DNA：Supercoils 1170
28.10 Replication of DNA 1172
28.11 Ribonucleic Acids 1172
RNA World 1177
28.12 Protein Biosynthesis 1178
28.13 AIDS 1179
28.14 DNA Sequencing 1180
28.15 The Human Genome Project 1182
28.16 DNA Profiling and the Polymerase Chain Reaction 1183
28.17 SUMMARY 1186
Problems 1189